{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nMitochondrial Complex I assembly and function rely on a coordinated interplay of multiple accessory proteins and chaperones. In models of Complex I dysfunction, mutations or deficiencies in key components—such as the accessory subunit NDUFS4—disrupt the normal assembly process, leading to severe tissue‐specific deficiencies. Loss of NDUFS4 causes near complete loss of the accessory subunit NDUFA12 and triggers a compensatory increase in the binding of the assembly factor/chaperone NDUFAF2 to inactive Complex I subcomplexes, suggesting that these proteins collectively function to stabilize or “rescue” Complex I assembly under pathological conditions."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "In related studies, deficiency of the Complex I‐associated factor NDUFAF2 in both neuroblastoma cells and primary fibroblasts from knockout mice results in a mature Complex I enzyme that nevertheless exhibits reduced enzymatic activity. These findings indicate that, distinct from other assembly factors that are essential for constructing the Complex I holoenzyme, NDUFAF2 acts more like a molecular chaperone: it is dispensable for the completion of assembly but is crucial for ensuring proper folding and full functional capacity of Complex I."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "A parallel line of investigation has identified a mitochondrial protein—mimitin—that appears to fulfill a similar chaperone-like role with respect to Complex I. Although not explicitly named PRR33 in these abstracts, mimitin functions analogously by regulating ATP synthesis and maintaining mitochondrial integrity. In pancreatic β-cells, overexpression of mimitin improves both basal and glucose-stimulated insulin secretion and protects against cytokine-induced toxicity by preventing caspase 3 activation and preserving mitochondrial membrane potential and ATP production; conversely, its knockdown exacerbates mitochondrial dysfunction. These properties underscore its role in modulating mitochondrial health and cellular resilience under inflammatory stress."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": ""}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Merel J W Adjobo-Hermans, Ria de Haas, Peter H G M Willems, et al. "}, {"type": "b", "children": [{"type": "t", "text": "NDUFS4 deletion triggers loss of NDUFA12 in Ndufs4"}, {"type": "a", "children": [{"type": "t", "text": "sup"}], "href": "sup"}, {"type": "t", "text": "-/-"}, {"type": "a", "children": [{"type": "t", "text": "/sup"}], "href": "/sup"}, {"type": "t", "text": " mice and Leigh syndrome patients: A stabilizing role for NDUFAF2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochim Biophys Acta Bioenerg (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbabio.2020.148213"}], "href": "https://doi.org/10.1016/j.bbabio.2020.148213"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32335026"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32335026"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Julia S Schlehe, Marion S M Journel, Kelsey P Taylor, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The mitochondrial disease associated protein Ndufaf2 is dispensable for Complex-1 assembly but critical for the regulation of oxidative stress."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neurobiol Dis (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.nbd.2013.05.007"}], "href": "https://doi.org/10.1016/j.nbd.2013.05.007"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23702311"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23702311"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Katarzyna Hanzelka, Lukasz Skalniak, Jolanta Jura, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Effects of the novel mitochondrial protein mimitin in insulin-secreting cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem J (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1042/BJ20111920"}], "href": "https://doi.org/10.1042/BJ20111920"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22587331"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22587331"}]}]}]}